PB2443: APPLICABILITY OF SHORT TANDEM REPEAT (STR) IN LEUKEMIA PATIENTS RECEIVED ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE ERA OF MINIMAL RESIDUAL DISEASE (MRD)
Authors: Juhyung Kim, Hee Jeong Cho, Dong Won Baek, Joon Ho Moon, Sang Kyun Sohn
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Dynamic monitoring chimerism by short tandem repeat PCR (STR-PCR) is of crucial importance for predicting graft rejection and disease relapse, and provides a basis for early clinical intervention in the patients received allo-hematopoietic stem cell transplantation (HSCT). After cancer treatment the number of tumor cells is remarkably low that it can only be recognized by extremely sensitive techniques, it is named minimal residual disease (MRD). MRD analysis with next generation sequencing (NGS), next generation flow cytometry (NGF), digital PCR (dPCR) and quantitative PCR (qPCR) could be used to overcome the technical limitation of STR-PCR, which achieves better sensitivity in comparison with STR-PCR in BM and PB. Nevertheless, these highly sensitive advanced techniques might not be consequential for regular chimerism analyses of blood or bone marrow samples, because of risk of contamination by recipient cells. Although there are numerous advanced techniques for capturing MRD status, they are not freely available for every patient, and STR-PCR is still used as a surrogate analysis tool. Aims: The current study aimed to evaluate the applicability of STR to monitoring of chimerism in patients who received HSCT in the era of MRD. Methods: We retrospectively analyzed data from 149 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic cell transplantation (allo-HCT) from February 2007 to November 2020. Patients between 14 and 79 years were included in the present study. STR-PCR was conducted with simple PCR coupled with capillary electrophoresis. Results: A total of 145 patients who underwent allo-HCT at Kyungpook National University Hospital were included in this study, and median age was 43.0 (range, 30-55) years. Patients diagnosed with AML were 89, and ALL were 56. Allo-HCT were conducted in CR1 (n = 105), CR2 (n=32) and refractory (n=8). After transplantation, 47 patients (32%) were relapsed. Mixed chimerism (MC) was detected in 19 patients (13%) according to STR-PCR using peripheral blood (PB). Among the 19 patients with mixed chimerism, 8 patients (5.5%) showed average >5% recipient DNA in PB, and five of them (62.5%) experienced disease relapse, while other 11 patients (57.9%) presented detectable but average of <5% recipient DNA in PB, and three of them (27%) showed relapse. Seven out of 8 relapsed patients with mixed chimerism did not stop the immunosuppressive agents due to graft-versus-host-disease (GVHD). Three patients with average of >5% recipient DNA in PB who stopped immunosuppression therapy did not relapse. In addition, five of 6 patients with average <5% recipient DNA in PB who discontinued immunosuppression therapy also did not show disease relapse. The only one patient who stopped the immunosuppression therapy showed the chloroma without overt bone marrow relapse. There was no significant PFS (progression-free survival) difference between complete chimerism group and mixed chimerism (allele < 5%) group, while there was considerable difference between complete chimerism group and mixed chimerism (allele >5%) group.Summary/Conclusion: Although it is likely that NGS could replace the STR-PCR analysis, it seems clear that STR-PCR still remains the gold standard option for chimerism study. As a surrogate marker, STR can still be used for predicting recurrence in patients with acute leukemia received allo-HCT. Furthermore, discontinuation of immunosuppressive agent can be an efficient method for preventing relapse in patients presenting mixed chimerism by STR. Keywords: Minimal residual disease (MRD), Survival prediction, Allogeneic hematopoietic stem cell transplant